Systemic lupus erythematosus is still a disease of unknown etiology. However, all available evidence supports the concept that it is an immune complex disease. The clinical manifestations of systemic lupus, as well as the renal involvement, are highly variable. Some patients have no renal involvement, others have mild glomerulonephritis, and some succumb to this manifestation of lupus in spite of available therapy. The reasons for these variations are not known. The objectives for this proposal are to clarify the mechanisms of renal immune complex deposition in experimental animals and to identify in lupus glomerulonephritis the antigens of immune complexes, localized in the mesangial, subepithelial and subendothelial areas. The work in mice will be conducted by injection of preformed immune complexes under various conditions, including prior chronic and acute injury to the mesangial and endothelial area, or local immune reaction with material deposited in the mesangium, and sequential administration of antigens and antibodies in single and multiple doses. Covalently crosslinked immune complexes will be prepared and complexes with discrete degrees of lattice formation will be isolated. The physiology of these preparations will be examined and their interaction with cell receptors and the first component of complement will be characterized. The origin of cells that constitute the increase in glomerular mesangial cells will be established. On renal biopsies of patients with lupus the antigens of immune complexes in glomeruli will be localized by immunoelectron microscopy. BIBLIOGRAPHIC REFERENCES: Haakenstad, A. O. and Mannik, M. The disappearance kinetics of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice. Lab. Invest. 35, 283-292, 1976. Haakenstad, A. O., Striker, G.E. and Mannik, M. The glomerular deposition of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice. Lab. Invest. 35, 2983-3001, 1976.